The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance

Chen, Kangchen; Zhang, Chenzhi; Ling, Sunbin; Wei, Ran; Wang, Jianguo; Xu, Xiao

doi:10.1038/s41419-021-04116-6

Cited by 57 publications

(35 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is another peculiar characteristic of CSCs that can give them the ability to be quiescent: plasticity. Cell plasticity allows for cellular switching in response to signals from the surrounding environment, without the need for genetic change, even modulating cell cycle entry and exit [ 57 , 78 ]. This mechanism lets cancer cells adapt better to circumstances, especially adverse conditions, and allows CSCs to facilitate cancer progression, remaining safe and quiescent for years, ready for awakening as soon as the situation requires rebuilding the tumor itself [ 79 , 80 ].…”

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

View full text Add to dashboard Cite

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

show abstract

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“… • The quiescent state : Quiescence or dormancy is a survival strategy for CSCs. In the quiescent state, cell division stops for a while, and cells live with minimal metabolic activity, but still retain the ability to reactivate the cell cycle ( Chen et al, 2021 ). In this state, both intrinsic (e.g., p53 signaling, reactive oxygen species, hypoxia inducible factor-1a, nuclear factor of activated T cells c1, and negative regulators of mTOR) and non-intrinsic factors (e.g., Tie2/angiopoietin-1, TGF-b and bone morphogenic proteins, thrombopoietin, N-cadherin and integrins, osteopontin, and Wnt/b-catenin signaling) are involved ( Li and Bhatia, 2011 ).…”

Section: The Biology Of Cancer Stem Cellsmentioning

confidence: 99%

“…According to studies, TME and epigenetic mechanisms have a major contribution to the maintenance of the quiescentstate of CSCs as well as evade immune surveillance and destruction, and tumor relapse. Therefore, the presence and persistence of the quiescence or dormancy state in CSCs can lead to the survival of CSCs and cell resistance to treatments such as chemotherapy ( Chen et al, 2021 ). • Self-renewal : Self-renewal is one of the noted hallmarks of CSCs that results from a malfunction of self-renewal pathways (SRPs).…”

Section: The Biology Of Cancer Stem Cellsmentioning

confidence: 99%

Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes

et al. 2022

View full text Add to dashboard Cite

Cancer stem cells (CSCs) are subpopulation of cells which have been demonstrated in a variety of cancer models and involved in cancer initiation, progression, and development. Indeed, CSCs which seem to form a small percentage of tumor cells, display resembling characteristics to natural stem cells such as self-renewal, survival, differentiation, proliferation, and quiescence. Moreover, they have some characteristics that eventually can demonstrate the heterogeneity of cancer cells and tumor progression. On the other hand, another aspect of CSCs that has been recognized as a central concern facing cancer patients is resistance to mainstays of cancer treatment such as chemotherapy and radiation. Owing to these details and the stated stemness capabilities, these immature progenitors of cancerous cells can constantly persist after different therapies and cause tumor regrowth or metastasis. Further, in both normal development and malignancy, cellular metabolism and stemness are intricately linked and CSCs dominant metabolic phenotype changes across tumor entities, patients, and tumor subclones. Hence, CSCs can be determined as one of the factors that correlate to the failure of common therapeutic approaches in cancer treatment. In this context, researchers are searching out new alternative or complementary therapies such as targeted methods to fight against cancer. Molecular docking is one of the computational modeling methods that has a new promise in cancer cell targeting through drug designing and discovering programs. In a simple definition, molecular docking methods are used to determine the metabolic interaction between two molecules and find the best orientation of a ligand to its molecular target with minimal free energy in the formation of a stable complex. As a comprehensive approach, this computational drug design method can be thought more cost-effective and time-saving compare to other conventional methods in cancer treatment. In addition, increasing productivity and quality in pharmaceutical research can be another advantage of this molecular modeling method. Therefore, in recent years, it can be concluded that molecular docking can be considered as one of the novel strategies at the forefront of the cancer battle via targeting cancer stem cell metabolic processes.

show abstract

“…The metabolic profile of dormant cells reflects the function they perform during tumorigenesis. In this line, data are still controversial about the differences between the metabolic states of quiescent CSCs and their differentiated progeny [180]. Indeed, although some studies report, as mentioned above, the dependence of CSCs quiescence on OXPHOS [181][182][183], some others describe a greater dependence on anaerobic glucose metabolism [184][185][186].…”

Section: Metabolic Adaptations Of Dormant Cscsmentioning

confidence: 99%

Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies

Pranzini

Raugei

Taddei

2022

Cancers

View full text Add to dashboard Cite

Tumor relapse represents one of the main obstacles to cancer treatment. Many patients experience cancer relapse even decades from the primary tumor eradication, developing more aggressive and metastatic disease. This phenomenon is associated with the emergence of dormant cancer cells, characterized by cell cycle arrest and largely insensitive to conventional anti-cancer therapies. These rare and elusive cells may regain proliferative abilities upon the induction of cell-intrinsic and extrinsic factors, thus fueling tumor re-growth and metastasis formation. The molecular mechanisms underlying the maintenance of resistant dormant cells and their awakening are intriguing but, currently, still largely unknown. However, increasing evidence recently underlined a strong dependency of cell cycle progression to metabolic adaptations of cancer cells. Even if dormant cells are frequently characterized by a general metabolic slowdown and an increased ability to cope with oxidative stress, different factors, such as extracellular matrix composition, stromal cells influence, and nutrient availability, may dictate specific changes in dormant cells, finally resulting in tumor relapse. The main topic of this review is deciphering the role of the metabolic pathways involved in tumor cells dormancy to provide new strategies for selectively targeting these cells to prevent fatal recurrence and maximize therapeutic benefit.

show abstract

The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance

Cited by 57 publications

References 122 publications

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Molecular Docking as a Therapeutic Approach for Targeting Cancer Stem Cell Metabolic Processes

Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies

Contact Info

Product

Resources

About